Several enzymes have different forms in surface and crypt cells of the intestines on the basis of heat stability, molecular size and electrophoretic properties. The enzymes of colon tumors seem to differ also and in the case of thymidine kinase (TK), at least, tumor form resembles the surface form immunologically. This could supply a rational basis for designs of tumor-specific antimetabolites. We plan to purify tumor and fetal cell crypt and flat mucosal enzymes. The several forms will be compared to determine changes that occur with differentiation and carcinogenesis. The observation that TK of mucosa of patients with carcinoma appears to differ with the extent of their disease will be further explored. Assays will be made on surgical specimens and course of patients followed. The basis for the low ornithine decarboxylase (ODC) levels in large as compared to small bowel and its regulation by c-AMP will be investigated. The phosphodiesterase in colon will be measured and parallels between it and ODC level with aging and exposure to carcinogens will be analyzed. The unusual repair of carcinogen-induced damage to the DNA of colonic surface mucosa will be studied to see if a relationship between the action of carcinogens on the surface is qualitatively or only quantitatively different. Time and dose response curves will be determined. Damage and post-repair uptake of BUdR followed by 313 nm radiation will be assayed. Changes with aging and exposure to carcinogens of HPRT, APRT, TK, thymidine phosphorylase, PRPP synthetase, ODC, PRPP amidotransferase, adenosine deaminase, inosine phosphorylase, T-RNA methylase and c-AMP phosphodiesterase and relevant substrates will also be measured. It is hoped that correlation of changes in these with changes seen in carcinogenic transformation of the large bowel will give information useful to diagnosis and prevention of carcinoma of the large bowel.